Article

Efficacy of simple short-term in vitro assays for predicting the potential of metal oxide nanoparticles to cause pulmonary inflammation.

University of Edinburgh, Edinburgh, UK.
Environmental Health Perspectives (Impact Factor: 7.26). 03/2009; 117(2):241-7. DOI: 10.1289/ehp.11811
Source: PubMed

ABSTRACT There has been concern regarding risks from inhalation exposure to nanoparticles (NPs). The large number of particles requiring testing means that alternative approaches to animal testing are needed.
We set out to determine whether short-term in vitro assays that assess intrinsic oxidative stress potential and membrane-damaging potency of a panel of metal oxide NPs can be used to predict their inflammogenic potency.
For a panel of metal oxide NPs, we investigated intrinsic free radical generation, oxidative activity in an extracellular environment, cytotoxicity to lung epithelial cells, hemolysis, and inflammation potency in rat lungs. All exposures were carried out at equal surface area doses.
Only nickel oxide (NiO) and alumina 2 caused significant lung inflammation when instilled into rat lungs at equal surface area, suggesting that these two had extra surface reactivity. We observed significant free radical generation with 4 of 13 metal oxides, only one of which was inflammogenic. Only 3 of 13 were significantly hemolytic, two of which were inflammogenic.
Potency in generating free radicals in vitro did not predict inflammation, whereas alumina 2 had no free radical activity but was inflammogenic. The hemolysis assay was correct in predicting the proinflammatory potential of 12 of 13 of the particles examined. Using a battery of simple in vitro tests, it is possible to predict the inflammogenicity of metal oxide NPs, although some false-positive results are likely. More research using a larger panel is needed to confirm the efficacy and generality of this approach for metal oxide NPs.

1 Bookmark
 · 
157 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1alpha, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.
    Particle and Fibre Toxicology 04/2014; 11(1):15. · 9.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the emerging issue of increased mult i-resistant properties in food borne pathogens, zinc o xide (Zn O) and nano-particle zinc o xide (nano-ZnO) are being used increasingly as antimicrobial agents. Thus, the min imu m inhibitory concentration (MIC) and minimu m bactericidal concentration (M BC) of nano -ZnO towards pathogens microbes Bacillus subtilus NRRL B-543, Bacillus megaterium ATCC 25848, Staphylococcus aureus; NRRL B-313, Sarcina lutea ATCC27853, Escherichia coli; NRRL B-210, Pseudomonas aeruginosa NRRL B23 27853, Klebsiella pneumoniae ATCC 27736, proteus vulgaris NRRL B-123, Candida albicans NRRL Y-477 and Aspergillus niger NRRL-3 were examined in this study. The results obtained suggested that nano-Zno exhib it a good bacteriostatic effect but poor bactericidal effect towards all pathogens tested. Nano-ZnO can be a potential antimicrobial agent due to its low cost of production and high effectiveness in antimicrobial p roperties, which may find wide applicat ions in various industries to address safety issues.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past two decades, there has been considerable research interest in the use of nanoparticles in the study of protein and peptide aggregation, and of amyloid-related diseases. The influence of nanoparticles on amyloid formation yields great interest due to its small size and high surface area-to-volume ratio. Targeting nucleation kinetics by nanoparticles is one of the most searched for ways to control or induce this phenomenon. The observed effect of nanoparticles on the nucleation phase is determined by particle composition, as well as the amount and nature of the particle's surface. Various thermodynamic parameters influence the interaction of proteins and nanoparticles in the solution, and regulate the protein assembly into fibrils, as well as the disaggregation of preformed fibrils. Metals, organic particles, inorganic particles, amino acids, peptides, proteins, and so on are more suitable candidates for nanoparticle formulation. In the present review, we attempt to explore the effects of nanoparticles on protein and peptide fibrillation processes from both perspectives (ie, as inducers and inhibitors on nucleation kinetics and in the disaggregation of preformed fibrils). Their formulation and characterization by different techniques have been also addressed, along with their toxicological effects, both in vivo and in vitro.
    International Journal of Nanomedicine 01/2014; 9:899-912. · 4.20 Impact Factor

Full-text (2 Sources)

View
26 Downloads
Available from
May 23, 2014